Pharmacological Reviews, Vol 6, 345-364, Copyright © 1954 by the American Society for Pharmacology and Experimental Therapeutics

MUTAGENS

¹ Chester Beatty Research Institute, Royal Cancer Hospital, London, S. W. S. England

One of the difficulties in the study of mutagenesis is the variability of the results obtained. Although radiations and the active vesicants are active on all systems which have been tested, urethane has no effect when tested on Neurospora reversions and ferrous chloride had been found active only when tested on bacteria. This variability makes the comparison with other effects very uncertain. This is particularly the case in the comparison with carcinogenesis, as cancer can be induced only in vertebrate animals and it is difficult, laborious and expensive to measure mutation rates in mammals or other vertebrates.

From the point of view of therapeutics mutagenic action is almost always a disadvantage. If a mutagenic agent is used in the treatment of infectious disease or leucaemia the drug is likely to induce mutant resistant forms. Thus a drug with mutagenic action is more likely to cause drug fastness to develop than is a drug without such action. An example of this is streptomycin which appears to be mutagenic for the tubercie bacillus (103).

The mechanism of mutagenic action which can be brought about by a wide variety of different chemical and physical agents is not known. That such a variety of means should operate through the same mechanism appears to be very unlikely. In the reviewer's opinion the mechanisms by which chromosome breakage, mutagenesis and careinogenesis are brought about by any one compound are probably similar, being different manifestations of the same effect. A number of possible mechanisms have been suggested for carcinogenic action (27) depending upon different effects on deoxyribonucleic acid of chromosomes and including modification and possibly destruction by irradiation or mustards, precipitation or increased gelation by metal salts, inhibition of synthesis by urethane or anti-metabolites and complex formation by polycyclic hydrocarbons and heterocyclic compounds.